Multiple sclerosis is not a disease of the immune system – Source: The Quarterly Review of Biology, Dec 23, 2011

Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system.

The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations.

Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease.

I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids [fatty acids].

Specifically, the homeostasis of lipid metabolism collapses during acute-phase inflammatory response triggered by a pathogen, trauma, or stress, starting a feedback loop of increased oxidative stress, inflammatory response [somewhat like what happens in hardening of the arteries], and proliferation of cytoxic foam cells that cross the blood brain barrier and both catabolize [break down] myelin and prevent remyelination [rebuilding of the nerve’s myelin sheath, damaged in MS].

Understanding MS as a chronic metabolic disorder illuminates four aspects of disease onset and progression:

Everyone should read this paper. However it understates the role of vitamin D particularly in gene damage and repair. Vitamin D levels below 30ng/ml is THE main environmental risk factor in MS.
The paper explains the role of PPARS but does not make a link between vitamin d insufficiency/deficiency and PPAR dysfunction. It hints at each being independent factors. I would like to see a follow up showing the link between PPAR dysfunction and vitamin D levels.

There is quite a significant amount of evidence that many common pthalates are synthetic ligands of these nuclear receptors. Some studies have been looking at the link between pthalates, PPAR function and obesity as well as more general endocrine dysfunction. We need to look at the role of pthalates, PPAR function and ME. Research by Myhill and by Bell have shown evidence that mitochondrial dysfunction is at the heart of ME but not a simple phosphorylation problem. Others have suggested a methylation problem. Pthalate interference of PPAR function in susceptible individuals would lead to the many varied symptoms of ME.